The activation of transforming growth factor alpha (TGFalpha)-erbB-1 and neuregulin-erbB-4 signaling pathways in hypothalamic astrocytes has been shown to play a key role in the process by which the neuroendocrine brain controls luteinizing hormone-releasing hormone (LHRH) secretion. Earlier studies suggested that tanycytes, an ependymoglial cell type of the median eminence, regulate LHRH relea...

Maspin is a unique member of the serpin family involved in regulation of cell migration, apoptosis and angiogenesis in breast and prostate cancers. In this study maspin expression in comparison with c-erbB-2 (HER2/neu) oncogene expression and microvessel density was investigated. The examined material included specimens of primary invasive ductal breast cancer derived from 69 patients. They wer...

PURPOSE The putative association between erbB-2 overexpression and favorable response to anthracyline-based therapy in breast cancer is controversial, and the mechanism unclear. We sought to determine whether coamplification and overexpression of the topoisomerase IIalpha gene, near erbB-2 on chromosome 17, and a known anthracycline target, may underlie the association. EXPERIMENTAL DESIGN Th...

We have analyzed genomic DNA sequences from 125 prospectively collected single unilateral primary breast carcinoma samples for the presence of alterations of c-myc, c-erbB-1, c-erbB-2, c-Ki-ras and c-Ha-ras protooncogenes. Amplification of the c-myc gene was found in 18% of the samples, and in one sample a non-germ line c-myc related DNA fragment or rearrangement was detected. We have found a s...

Integral membrane proteins contain a hydrophobic transmembrane domain and mainly locate in the plasma membrane lipid bilayer. The receptor tyrosine kinases (RTK) of the epidermal growth factor receptor (EGFR) superfamily, including ErbB-1, ErbB-2, ErbB-3, and ErbB-4, constitute an important group of such membrane proteins, which have a profound impact on cancer initiation, progression, and pati...

The introduction of the so-called "targeted therapies", particularly those drugs that inhibit the activity of tyrosine kinases, has represented a remarkable progress in the treatment of cancer. Although these drugs improve survival rates in cancer, significant cardiotoxicity, manifesting as left vertricular dysfunction and/or heart failure, has emerged. The ErbB receptor tyrosine kinases are be...

ErbB family members represent important biomarkers and drug targets for modern precision therapy. They have gained considerable importance as paradigms for oncoprotein addiction and personalized medicine. This review summarizes the current understanding of ErbB proteins in cell signalling and cancer and describes the molecular rationale of prominent cases of ErbB oncoprotein addiction in differ...

The ErbB signaling module consists of four receptor tyrosine kinases and several dozen ligands that activate specific homo- and heterodimeric complexes of ErbB proteins. Combinatorial ligand/receptor/effector interactions allow large potential for signal diversification. Here we addressed the possibility that turn-off mechanisms enhance the diversification potential. Concentrating on ErbB-1 and...

Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor-2 (HER2/ErbB-2), has become the mainstay of treatment for HER2-positive breast cancer. Nevertheless, its exact mechanism of action has not been fully elucidated. Although several studies suggest that Fc receptor-expressing immune cells are involved in trastuzumab therapy, the relative contribution of lymphocyte-...

Amplification and/or overexpression of the erbB-2 gene have been demonstrated in 20-30% of adenocarcinomas of the breast, ovary, lung, and stomach and are associated with aggressive clinical course and poor prognosis. Interference with erbB-2 function by the use of monoclonal antibodies is a promising approach to the treatment of these diseases. In this study we demonstrate that a combination o...